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Dynamic changes in the expression of DEP-1 and other PDGF receptor-antagonizing PTPs during onset and termination of

Kai Kappert1, Janna Paulsson, Jan Sparwel

  • 1Cancer Centrum Karolinska, Department of Oncology-Pathology, Karolinska Institutet, 17176 Stockholm, Sweden.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|December 13, 2006
PubMed

Insights

Protein-tyrosine-phosphatases (PTPs), particularly DEP-1, are key regulators of platelet-derived growth factor receptor (PDGF) signaling and vascular smooth muscle cell proliferation, controlling tissue remodeling processes like restenosis.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cardiovascular Research

Background:

  • Tissue remodeling, including restenosis, is primarily regulated by receptor-tyrosine-kinases (RTKs) and their ligands.
  • Protein-tyrosine-phosphatases (PTPs) act as endogenous antagonists of RTKs, suggesting their role in regulating these processes.

Purpose of the Study:

  • To investigate the layer-specific expression of PDGF isoforms, PDGF receptors, and PTPs after balloon injury in rat carotid arteries.
  • To correlate PTP expression with PDGF-beta receptor phosphorylation and vascular smooth muscle cell (VSMC) proliferation in vivo.

Main Methods:

  • Laser-capture-microdissection and quantitative RT-polymerase chain reaction (qRT-PCR) for gene expression analysis.
  • Analysis of PDGF-beta receptor phosphorylation and VSMC proliferation in vivo.
  • In vitro studies using DEP-1 knockout cells and siRNA-mediated knockdown in VSMCs.

Main Results:

  • Component expression, receptor activation, and VSMC proliferation exhibited layer-specific changes between media and neointima.
  • PTP expression, especially DEP-1, significantly influenced PDGF-receptor phosphorylation and VSMC proliferation.
  • DEP-1 deficiency or knockdown led to increased PDGF-dependent cell signaling and hyperactivation of PDGF-induced signaling.

Conclusions:

  • PDGF-receptor-targeting PTPs play a crucial, previously unrecognized role in neointima formation.
  • Transcriptional regulation of PTPs is a significant mechanism controlling the initiation and cessation of RTK-dependent tissue remodeling.

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